The applicant plans to study the retinoblastoma gene theorized to be on the q14 band of chromosone 13. Until now, the main evidence for this gene localization is a set of publication over the past 20 years describing sporadic retinoblastoma patients with deletions involving 13q14. The project will use two different approaches to test whether the gene for familial retinoblastoma is also on 13q14. First, the applicant will examine esterase-D allels, known to be in the vicinity of 13q14, in families with retinoblastoma. In a given family, linkage of a given allele with the presence of retinoblastoma will be good evidence for gene localization to 13q14. Secondly, by using a combination of somatic cell hybridization and recombinant DNA technologies, the applicant hopes to find DNA polymorphisms less that 5 million base pairs from the hypothetical gene. These polymorphisms will serve as an excellent tool for genetic counseling in familial retinoblastoma, as well as an ideal starting point for any future studies aimed at characterizing the retinoblastoma gene itself.